Journal: Scientific Reports

Article Title: Valosin-containing protein modulator KUS121 protects retinal neurons in a rat model of anterior ischemic optic neuropathy

doi: 10.1038/s41598-025-99287-z

Figure Lengend Snippet: Effects of pre-intravitreal injection of KUS121 in a rat model of anterior ischemic optic neuropathy (rAION). a Schematic of the experimental schedule. AION: anterior ischemic optic neuropathy, OCT: optical coherent tomography, HE: hematoxylin eosin-staining, IVT: intravitreal injection. b , c Retinal thickness, including the retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL), (b) and its percent change compared to pre-treatment value (c) in AION rats intravitreally injected with KUS121 ( n = 10, squares) or vehicle (control) ( n = 8, circles). Error bars indicate standard error (SE). ** P < 0.01, *** P < 0.001 vs. control (Student’s t -test), ### P < 0.001 vs. control (Aspin–Welch’s t -test). d–f Representative OCT images of wild-type rats (WT, d) and AION rats injected with vehicle (control, e) or KUS121 (f). The double arrows indicate the layers, including the RNFL and GCL. Bar = 200 μm. g–i Representative images of HE-stained retinal sections of WT rats (WT, g) and AION rats injected with vehicle (control, h) or KUS121 (i). IPL: inner plexiform layer, INL: inner nuclear layer, OPL: outer plexiform layer, ONL: outer nuclear layer, RPE: retinal pigment epithelium. Bar = 50 μm. j–l Representative images of flat-mounted retinas of WT (j) and AION rats injected with vehicle (control, k) or KUS121 (l) at 28 days post-AION induction. Bar = 100 μm. m Number of GFP-positive retinal ganglion cells (RGCs) in WT ( n = 10) and AION rats injected with vehicle (control, n = 8) or KUS121 ( n = 10) at 28 days post-AION induction. GFP-positive RGCs were manually counted within four 500-µm squares located 2000 μm from the optic nerve head center (supplementary Fig. f). Bars indicate average. *** P < 0.001 vs. WT, # P = 0.021 vs. control (Tukey’s HSD test).

Article Snippet: Ischemic optic neuropathy (ION) is a major cause of vision impairment and is classified into anterior ischemic optic neuropathy (AION) and posterior ischemic optic neuropathy (PION) .

Techniques: Injection, Tomography, Staining, Control

Journal: Scientific Reports

Article Title: Valosin-containing protein modulator KUS121 protects retinal neurons in a rat model of anterior ischemic optic neuropathy

doi: 10.1038/s41598-025-99287-z

Figure Lengend Snippet: Effects of post-induction intravitreal injections of KUS121 in a rat model of anterior ischemic optic neuropathy (rAION). a Schematic of experimental schedule. IVT: intravitreal injection. b , c Thickness of retinal layers, including the RNFL and GCL, ( b ) and the percent change compared to pre-treatment value ( c ) in AION rats injected with vehicle (control, n = 8, circles) or KUS121 ( n = 8, squares). Error bars indicate SE. ** P < 0.01 vs. control (Student’s t -test). d–f Representative OCT images of wild-type (WT, d) and AION rats injected with vehicle (control, e ) or KUS121 ( f ). The double arrows indicate the layers, including the RNFL and GCL. Bar = 200 μm. g–i Representative HE-stained retinal sections of WT ( g ) and AION rats injected with vehicle (control, h) or KUS121 (i) at 28 days post-AION induction. Bar = 50 μm. j–l Representative images of flat-mounted retinas of WT (j) and AION rats injected with vehicle (control, k) or KUS121 ( l ) at 28 days post-AION induction. Bar = 100 μm. m Number of GFP-positive RGCs in flat-mounted retinas of WT ( n = 10) and AION rats injected with vehicle (control, n = 10) or KUS121 ( n = 7) at 28 days post-AION induction. GFP-positive RGCs were manually counted within four 500-µm squares located 2000 μm from the optic nerve head center (supplementary Fig. f). Bars indicate average. *** P < 0.001 vs. WT (Tukey’s HSD test).

Article Snippet: Ischemic optic neuropathy (ION) is a major cause of vision impairment and is classified into anterior ischemic optic neuropathy (AION) and posterior ischemic optic neuropathy (PION) .

Techniques: Injection, Control, Staining

Journal: Scientific Reports

Article Title: Valosin-containing protein modulator KUS121 protects retinal neurons in a rat model of anterior ischemic optic neuropathy

doi: 10.1038/s41598-025-99287-z

Figure Lengend Snippet: Protective effect of KUS121 on the optic nerve of a rat model of anterior ischemic optic neuropathy (rAION). Histological examination of optic nerve sections in wild-type (WT), vehicle-treated AION (control), and KUS121-treated AION (KUS121) rats 28 days post-AION induction. Images of hematoxylin–eosin (HE)-stained sections ( a ); sections immunostained with anti-macrophage (ED1) ( b ), glial fibrillary acidic protein (GFAP) ( c ), ionized calcium-binding adapter molecule 1 (Iba1) ( d ), and neurofilament ( e ); and sections stained with Klüver–Barrera (KB) solution ( f ). Cells were counterstained with hematoxylin or cresyl violet. Bar = 50 μm. See Supplementary Fig. for low-magnification images. g-i Number of ED1-positive cells (g, WT: 1.3 ± 0.8 cells, control: 217.8 ± 14.6 cells, KUS121: 51.7 ± 20.2 cells), and proportion of GFAP- ( h , WT: 9.3 ± 0.9%, control: 24.1 ± 1.4%, KUS121: 16.7 ± 1.4%) and Iba1-stained areas (I, WT: 2.7 ± 0.4%, control: 7.6 ± 0.2%, KUS121: 3.4 ± 0.3%). WT: n = 3, control: n = 4, KUS121: n = 3 in g, n = 4 in h, i. Bars indicate average. * P < 0.05, ** P < 0.01, *** P < 0.001, WT vs. control (Tukey’s HSD test), ## P < 0.01 control vs. KUS121 (Tukey’s HSD test).

Article Snippet: Ischemic optic neuropathy (ION) is a major cause of vision impairment and is classified into anterior ischemic optic neuropathy (AION) and posterior ischemic optic neuropathy (PION) .

Techniques: Control, Staining, Binding Assay

Journal: Scientific Reports

Article Title: Valosin-containing protein modulator KUS121 protects retinal neurons in a rat model of anterior ischemic optic neuropathy

doi: 10.1038/s41598-025-99287-z

Figure Lengend Snippet: KUS121 ameliorates myelin degeneration in the optic nerve of rats with anterior ischemic optic neuropathy (AION). Electron microscopy images of the optic nerve of wild-type (WT, a , b ), vehicle-treated (control, c , d ), and KUS121-treated rats (KUS121, e , f ) 56 days post-AION induction. The arrowheads indicate myelin sheath thickening and arrows indicate myelin sheath expansion. Bar = 5000 nm in (a), (c), and (e); 500 nm in (b), (d), and (f). (g) Myelin sheaths were counted per image in an area of 746 µm 2 . h Myelin sheath thickness was measured for 10 individual myelin sheaths per image in an area of 11 µm 2 , and the average thickness was calculated. Thickness of myelin sheaths: WT: 89.2 ± 2.3 nm, control: 158.1 ± 4.6 nm, KUS121: 130.7 ± 6.2 nm.** P < 0.01 (Tukey’s HSD test), n = 4. Bars indicate average.

Article Snippet: Ischemic optic neuropathy (ION) is a major cause of vision impairment and is classified into anterior ischemic optic neuropathy (AION) and posterior ischemic optic neuropathy (PION) .

Techniques: Electron Microscopy, Control

Journal: Scientific Reports

Article Title: Valosin-containing protein modulator KUS121 protects retinal neurons in a rat model of anterior ischemic optic neuropathy

doi: 10.1038/s41598-025-99287-z

Figure Lengend Snippet: KUS121 suppresses endoplasmic reticulum stress in rats with anterior ischemic optic neuropathy (AION). a , b Western blotting for C/EBP homologous protein (CHOP) and beta-actin expression in the retina before, and 1, 3 and 5 days post-AION induction (each group, n = 3). Complete scans of western blots are shown in Supplementary Fig. . Bars indicate average. * P < 0.05, vs. vehicle-treated AION rat (Tukey’s multiple comparison test). c-f CHOP immunostaining (red) at 1 (c, d) and 5 days ( e , f ) post-AION induction. The nuclei were counterstained with 4’,6-diamidino-2-phenylindole (DAPI, blue). d , f Comparison of average fluorescence intensity in the RNFL+GCL at 1 (d) and 5 days (f) post-AION induction. Student’s t -test. Bars indicate average. (each group, n = 3). WT: normal rat, C: vehicle-treated AION rat, KUS121: KUS121-treated AION rat. Bar = 100 μm.

Article Snippet: Ischemic optic neuropathy (ION) is a major cause of vision impairment and is classified into anterior ischemic optic neuropathy (AION) and posterior ischemic optic neuropathy (PION) .

Techniques: Western Blot, Expressing, Comparison, Immunostaining, Fluorescence